Clinical Trials List
Protocol NumberA928-CLN-001
NCT Number(ClinicalTrials.gov Identfier)NCT05687682
2023-04-01 - 2026-03-31
Phase I
Not yet recruiting3
A Phase I, Open-Label, Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AM-928 Infusion in Subjects With Advanced Solid Tumors
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Trial Applicant
A2 HEALTHCARE TAIWAN CORPORATION
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Sponsor
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Trial scale
Taiwan Multiple Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- HUAI-CHENG HUANG Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- 梁逸歆 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Hsiang-Fong Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 劉奕廷 Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Chun-Hui Lee Division of Hematology & Oncology
- Peng-Chan Lin Division of Hematology & Oncology
- 蘇勇曄 Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Shang-Hung Chen Division of Hematology & Oncology
- 顏志傑 Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- 黃盈慈 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Advanced Solid Tumor
Objectives
main purpose:
By defining the manifestation of dose-limiting toxicity, determine the maximum tolerated dose or maximum dose of AM-928
Secondary purpose:
To evaluate the safety, tolerability, pharmacokinetic (PK) profile and preliminary efficacy of AM-928 in subjects with advanced solid tumors
Exploratory purpose:
1. Evaluate the immunogenicity of AM-928 in subjects with advanced solid tumors
2. Characterize the expression of pharmacodynamic markers in the tumor microenvironment (if applicable)
3. Explore subject plasma tumor biomarkers altered by trial treatment (if applicable)
4. To explore the effect of AM-928 on clinical symptom relief
Test Drug
AM-928
Active Ingredient
AM-928
Dosage Form
Injections
Dosage
20 mg/ml
Endpoints
Maximum tolerated dose (or maximum administered dose) and dose-limiting toxicities
Inclution Criteria
Inclusion Criteria:
Male or female, age ≥ 18 years
Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors that are refractory to or intolerant of existing standard therapy, for which no effective standard therapy that confers clinical benefit is available
Availability of archival tissue specimens for EpCAM immunohistochemistry (IHC) staining. Tumor tissues acceptable include:
- Tumor tissue sample collected at the time of initial diagnosis
- The most recent available metastatic tumor biopsy tissue if available (a pre-treatment biopsy may be obtained if the biopsy site is safely accessible)
Has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
Subject's life expectancy of at least 12 weeks
Has adequate hematopoietic, coagulation, hepatic function and renal function:
- Hemoglobin ≥ 8.0 g/dL without transfusion or erythropoiesis stimulating agent support within 1 week
Absolute neutrophil count (ANC) ≥ 1,500 cells/μL without WBC growth factor support within 1 week
Total white blood cell (WBC) ≥ 2,500 cells/μL
Platelet ≥ 80,000 counts/μL without transfusion support within 1 week
International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 upper limit of normal (ULN)
Total bilirubin ≤ 1.5× ULN and no sign of jaundice (≤ 3× ULN for subjects with known Gilbert disease)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3× ULN (≤ 5× ULN for subjects with tumor involvement in liver)
Serum albumin ≥ 3.0 g/dL
eGFR (CKD-EPI) ≥ 60 mL/min/1.73 m^2
A female subject with childbearing potential should be confirmed of not being pregnant or not lactating at the screening and during the study
Willingness and ability to comply with protocol-stated requirements, instructions, and restrictions in the investigator's judgement
Is able to understand the nature of this study and accepts to enter the study by signing written informed consent
Male or female, age ≥ 18 years
Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors that are refractory to or intolerant of existing standard therapy, for which no effective standard therapy that confers clinical benefit is available
Availability of archival tissue specimens for EpCAM immunohistochemistry (IHC) staining. Tumor tissues acceptable include:
- Tumor tissue sample collected at the time of initial diagnosis
- The most recent available metastatic tumor biopsy tissue if available (a pre-treatment biopsy may be obtained if the biopsy site is safely accessible)
Has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
Subject's life expectancy of at least 12 weeks
Has adequate hematopoietic, coagulation, hepatic function and renal function:
- Hemoglobin ≥ 8.0 g/dL without transfusion or erythropoiesis stimulating agent support within 1 week
Absolute neutrophil count (ANC) ≥ 1,500 cells/μL without WBC growth factor support within 1 week
Total white blood cell (WBC) ≥ 2,500 cells/μL
Platelet ≥ 80,000 counts/μL without transfusion support within 1 week
International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 upper limit of normal (ULN)
Total bilirubin ≤ 1.5× ULN and no sign of jaundice (≤ 3× ULN for subjects with known Gilbert disease)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3× ULN (≤ 5× ULN for subjects with tumor involvement in liver)
Serum albumin ≥ 3.0 g/dL
eGFR (CKD-EPI) ≥ 60 mL/min/1.73 m^2
A female subject with childbearing potential should be confirmed of not being pregnant or not lactating at the screening and during the study
Willingness and ability to comply with protocol-stated requirements, instructions, and restrictions in the investigator's judgement
Is able to understand the nature of this study and accepts to enter the study by signing written informed consent
Exclusion Criteria
Exclusion Criteria:
Received any localized cancer therapeutic modalities (e.g., surgery on target lesions, radiotherapy) within 4 weeks prior to initial dosing (except the palliative radiotherapy performed on non-target local lesions), or have any unrecovered surgical wound (except the wound from the biopsy at screening)
Received anti-tumor chemotherapy, small molecular targeted therapy, hormone therapy (except hormone replacement therapy or oral contraceptives), biological product therapy (mAbs, bispecific antibody, and ADC), or other anti-cancer agents within 2 weeks or 5 half-lives (whichever is shorter) before the first AM-928 dosing; received immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) before the first AM-928 dosing.
Carries history of primary malignancy other than the entry diagnosis that could affect compliance with the protocol or interpretation of results within 3 years prior to the Screening Visit, except curatively treated non-melanoma skin cancer, cervical carcinoma in situ, or superficial bladder tumors
Received immunosuppressive medication(s) (including, but not limited to, steroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tumor necrosis factor-ɑ antagonists, and calcineurin inhibitors) within 2 weeks (for those half-life ≤ 72 hours) or 4 weeks (for those half-life > 72 hours) prior to study dosing and during the study period, with the following caveats:
- For steroids, ≤10 mg of prednisone per day or equivalent is allowed
Topical, ocular, intra-articular, intranasal, and inhaled corticosteroids is allowed. For a subject under long-term treatment of a concurrent disease/status, the dose should be stable (i.e., no change or decreasing dose) within 3 months prior to C1D1
The use of inhaled corticosteroids is allowed if they are on a stable dose (i.e., no change or decreasing dose within 3 months prior to C1D1)
The use of oral mineralocorticoids is allowed
Physiologic doses of corticosteroids for adrenal insufficiency or supportive care for a subject's advanced tumor may be allowed at the investigator's discretion
Subject with significant cardiopulmonary abnormalities as defined by:
Poorly controlled hypertension (systolic blood pressure > 150 mm-Hg and/or diastolic blood pressure > 100 mm-Hg on anti-hypersensitive medications)
Left ventricular ejection fraction (LVEF) < 50% at screening
History of symptomatic congestive heart failure > class 2 per New York Heart Association (NYHA) classification
History of myocarditis
Myocardial ischemia/infarction or unstable angina within 6 months of study enrollment
Uncontrolled serious cardiac arrhythmias
Corrected QT interval > 470 ms demonstrated by at least 2 ECGs > 30 minutes apart
Evidence of active pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or history of idiopathic pulmonary fibrosis. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
History of 2nd or 3rd-degree atrioventricular conduction defects
History of thromboembolic or cerebrovascular events within the last 6 months at screening, including transient ischemic attack, cerebrovascular accident, or deep vein thrombosis
Prior treatment with any EpCAM-targeted anti-cancer therapies
Subjects with the following infections:
- History of active pulmonary tuberculosis infection ≤ 48 weeks prior to C1D1, regardless of treatment
Any major episode of infection requiring treatment with systemic antibiotics or hospitalization within 2 weeks prior to C1D1
Known human immunodeficiency virus (HIV) history
Presence of hepatitis B surface antigen (HBsAg) with HBV viral load > 2000 IU/mL (HBsAg-positive subjects with HBV viral load ≤ 2000 IU/mL are eligible. These subjects should continue to receive antiviral treatment during the study treatment and follow local HBV antiviral treatment standards after the study treatment during the study)
HCV RNA positive (subjects with a history of HCV infection are eligible if their HCV viral load cannot be detected at screening; curative antiviral therapy should have been completed at least 4 weeks before C1D1)
Administration of a live, attenuated vaccine within 4 weeks before C1D1 or anticipation that such a live, attenuated vaccine will be required during the study
Received any investigational product within 4 weeks before C1D1
History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized antibodies
Known hypersensitivity to any of the components of AM-928
Has unstable/uncontrolled central nervous system (CNS) malignancy, leptomeningeal, or brain metastasis (progressing or those who continue to require glucocorticoids or intrathecal chemotherapy)
Has symptomatic pleural effusion, pericardial effusion, or poorly controlled ascites
Suffering from side/toxic effects of previous or current therapy [i.e., National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE) ≥ Grade 2] that, judged by the investigator, may interfere with the trial results or the subject's safety
Prior allogeneic stem cell, solid organ, or bone marrow transplantation
Subject with any underlying medical, mental, or psychological conditions that would impair the treatment compliance, contraindicate the use of the investigational product, or that may render the subject at high risk from treatment complications, in the opinion of the investigator, would not permit to participate in the study
All male subjects and female subjects with childbearing potential (between puberty and 1 year after menopause) should use at least one of the appropriate contraception methods shown below from signing ICF to at least 4 months or 5 half-lives (if data available), whichever is longer, after stopping study treatment.
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject.
Combination of any two of the following listed methods: (d.1+d.2 or d.1+d.3, or d.2+d.3):
d.1. Use oral, injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception.
d.2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). d.3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
Received any localized cancer therapeutic modalities (e.g., surgery on target lesions, radiotherapy) within 4 weeks prior to initial dosing (except the palliative radiotherapy performed on non-target local lesions), or have any unrecovered surgical wound (except the wound from the biopsy at screening)
Received anti-tumor chemotherapy, small molecular targeted therapy, hormone therapy (except hormone replacement therapy or oral contraceptives), biological product therapy (mAbs, bispecific antibody, and ADC), or other anti-cancer agents within 2 weeks or 5 half-lives (whichever is shorter) before the first AM-928 dosing; received immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) before the first AM-928 dosing.
Carries history of primary malignancy other than the entry diagnosis that could affect compliance with the protocol or interpretation of results within 3 years prior to the Screening Visit, except curatively treated non-melanoma skin cancer, cervical carcinoma in situ, or superficial bladder tumors
Received immunosuppressive medication(s) (including, but not limited to, steroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tumor necrosis factor-ɑ antagonists, and calcineurin inhibitors) within 2 weeks (for those half-life ≤ 72 hours) or 4 weeks (for those half-life > 72 hours) prior to study dosing and during the study period, with the following caveats:
- For steroids, ≤10 mg of prednisone per day or equivalent is allowed
Topical, ocular, intra-articular, intranasal, and inhaled corticosteroids is allowed. For a subject under long-term treatment of a concurrent disease/status, the dose should be stable (i.e., no change or decreasing dose) within 3 months prior to C1D1
The use of inhaled corticosteroids is allowed if they are on a stable dose (i.e., no change or decreasing dose within 3 months prior to C1D1)
The use of oral mineralocorticoids is allowed
Physiologic doses of corticosteroids for adrenal insufficiency or supportive care for a subject's advanced tumor may be allowed at the investigator's discretion
Subject with significant cardiopulmonary abnormalities as defined by:
Poorly controlled hypertension (systolic blood pressure > 150 mm-Hg and/or diastolic blood pressure > 100 mm-Hg on anti-hypersensitive medications)
Left ventricular ejection fraction (LVEF) < 50% at screening
History of symptomatic congestive heart failure > class 2 per New York Heart Association (NYHA) classification
History of myocarditis
Myocardial ischemia/infarction or unstable angina within 6 months of study enrollment
Uncontrolled serious cardiac arrhythmias
Corrected QT interval > 470 ms demonstrated by at least 2 ECGs > 30 minutes apart
Evidence of active pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or history of idiopathic pulmonary fibrosis. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
History of 2nd or 3rd-degree atrioventricular conduction defects
History of thromboembolic or cerebrovascular events within the last 6 months at screening, including transient ischemic attack, cerebrovascular accident, or deep vein thrombosis
Prior treatment with any EpCAM-targeted anti-cancer therapies
Subjects with the following infections:
- History of active pulmonary tuberculosis infection ≤ 48 weeks prior to C1D1, regardless of treatment
Any major episode of infection requiring treatment with systemic antibiotics or hospitalization within 2 weeks prior to C1D1
Known human immunodeficiency virus (HIV) history
Presence of hepatitis B surface antigen (HBsAg) with HBV viral load > 2000 IU/mL (HBsAg-positive subjects with HBV viral load ≤ 2000 IU/mL are eligible. These subjects should continue to receive antiviral treatment during the study treatment and follow local HBV antiviral treatment standards after the study treatment during the study)
HCV RNA positive (subjects with a history of HCV infection are eligible if their HCV viral load cannot be detected at screening; curative antiviral therapy should have been completed at least 4 weeks before C1D1)
Administration of a live, attenuated vaccine within 4 weeks before C1D1 or anticipation that such a live, attenuated vaccine will be required during the study
Received any investigational product within 4 weeks before C1D1
History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized antibodies
Known hypersensitivity to any of the components of AM-928
Has unstable/uncontrolled central nervous system (CNS) malignancy, leptomeningeal, or brain metastasis (progressing or those who continue to require glucocorticoids or intrathecal chemotherapy)
Has symptomatic pleural effusion, pericardial effusion, or poorly controlled ascites
Suffering from side/toxic effects of previous or current therapy [i.e., National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE) ≥ Grade 2] that, judged by the investigator, may interfere with the trial results or the subject's safety
Prior allogeneic stem cell, solid organ, or bone marrow transplantation
Subject with any underlying medical, mental, or psychological conditions that would impair the treatment compliance, contraindicate the use of the investigational product, or that may render the subject at high risk from treatment complications, in the opinion of the investigator, would not permit to participate in the study
All male subjects and female subjects with childbearing potential (between puberty and 1 year after menopause) should use at least one of the appropriate contraception methods shown below from signing ICF to at least 4 months or 5 half-lives (if data available), whichever is longer, after stopping study treatment.
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject.
Combination of any two of the following listed methods: (d.1+d.2 or d.1+d.3, or d.2+d.3):
d.1. Use oral, injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception.
d.2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). d.3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
The Estimated Number of Participants
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Taiwan
38 participants
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Global
38 participants
